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Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo

Anderson, L; Burnstein, RM; He, XL; Luce, R; Furlong, R; Foltynie, T; Sykacek, P; ... Caldwell, MA; + view all (2007) Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo. EXP NEUROL , 204 (2) 512 - 524. 10.1016/j.expneurol.2006.12.025.

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Abstract

Numerous cell culture protocols have been described for the proliferation of multipotent human neural progenitor cells (HNPCs). The mitogen combinations used to expand HNPCs vary, and it is not clear to what extent this may affect the subsequent differentiation of these cells. In this study human foetal cortical tissue was cultured in the presence of either EGF, or FGF-2, or a combination of both using a unique chopping method in which cell to cell contact is maintained. The differentiation potential of neurospheres following mitogen withdrawal was assessed at early (8 weeks) and late (20 weeks) times of expansion, both in vitro and in vivo. In addition, changes in gene expression with time were analysed by microarray experiments. Results show that the presence of FGF-2 was highly predictive of neuronal differentiation after short term culture both in vitro and in vivo. In addition, time in culture had a significant effect on transplant size and neural constituents suggesting that cells have a limited life span and restricted lineage potential. Array analysis confirms that following extensive time in culture cells are entering growth arrest with fundamental expression changes in genes associated with cell cycle regulation, apoptosis and immune functions. (c) 2007 Elsevier Inc. All rights reserved.

Type: Article
Title: Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo
DOI: 10.1016/j.expneurol.2006.12.025
Keywords: EGF, FGF-2, neural stem cells, microarray, human, p21, galectin-1, EPIDERMAL-GROWTH-FACTOR, CENTRAL-NERVOUS-SYSTEM, ADULT-RAT BRAIN, HUMAN FETAL-BRAIN, STEM-CELLS, PRECURSOR CELLS, DIFFERENTIATION FACTOR, NEUROTROPHIC FACTOR, PARKINSONS-DISEASE, HUMAN NEUROSPHERES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/106078
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